AIM:To elucidate the sequential transfer of iron amongst ferritin,transferrin and transferrin receptor under various iron status conditions.METHODS:Incorporation of 59Fe into mucosal and luminal proteins was carried out in control WKY rats.The sequential transfer of iron amongst ferritin,transferrin and transferrin receptor was carried out in iron deficient,control and iron overloaded rats.The duodenal proteins were subjected to immunoprecipitation and quantitation by specific ELISA and in situ localization by microautoradiography and immunohistochemistry in tandem duodenal sections.Human duodenal biopsy(n = 36)collected from subjects with differing iron status were also stained for these proteins.RESULTS:Ferritin was identified as the major protein that incorporated iron in a time-dependent manner in the duodenal mucosa.The concentration of mucosal ferritin was significantly higher in the iron excess group compared to control,iron deficient groups(731.5 ± 191.96 vs 308.3 ± 123.36,731.5 ± 191.96 vs 256.0 ± 1.19,P ＜ 0.005),while that of luminal transferrin which was significantly higher than the mucosal did not differ among the groups(10.9 ± 7.6 vs 0.87 ± 0.79,11.1 ± 10.3 vs 0.80 ± 1.20,6.8 ± 4.7 vs 0.61 ± 0.63,P ＜ 0.001).In situ grading of proteins and iron,and their superimposition,suggested the occurrence of a sequential transfer of iron.This was demonstrated to occur through the initial binding of iron to luminal transferrin then to absorptive cell surface transferrin receptors.The staining intensity of these proteins varied according to the iron nutrition in humans,with intense staining of transferrin receptor observed in iron deficient subjects.CONCLUSION:It is concluded that the intestine takes up iron through a sequential transfer involving interaction of luminal transferrin,transferrin-transferrin receptor and ferritin.